SB-334867   Click here for help

GtoPdb Ligand ID: 1703

Synonyms: SB-334,867 | SB334867 | SB334867A
PDB Ligand
Compound class: Synthetic organic
Comment: SB‐334867 is a selective OX1R antagonist. Selective OX1R blockade is suggested as a pharmacological mechanism that offers clinical utility for the treatment of addiction or anxiety disorders [5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

SB-334867 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 92.94
Molecular weight 319.11
XLogP 0.84
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=C(Nc1ccnc2c1nccc2)Nc1ccc2c(c1)oc(n2)C
Isomeric SMILES O=C(Nc1ccnc2c1nccc2)Nc1ccc2c(c1)oc(n2)C
InChI InChI=1S/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23)
InChI Key AKMNUCBQGHFICM-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Bonaventure P, Yun S, Johnson PL, Shekhar A, Fitz SD, Shireman BT, Lebold TP, Nepomuceno D, Lord B, Wennerholm M et al.. (2015)
A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects.
J Pharmacol Exp Ther, 352 (3): 590-601. [PMID:25583879]
2. Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ. (2004)
Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor.
Br J Pharmacol, 141 (2): 340-6. [PMID:14691055]
3. Malherbe P, Borroni E, Gobbi L, Knust H, Nettekoven M, Pinard E, Roche O, Rogers-Evans M, Wettstein JG, Moreau JL. (2009)
Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor.
Br J Pharmacol, 156 (8): 1326-41. [PMID:19751316]
4. Malherbe P, Borroni E, Pinard E, Wettstein JG, Knoflach F. (2009)
Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists.
Mol Pharmacol, 76 (3): 618-31. [PMID:19542319]
5. Merlo Pich E, Melotto S. (2014)
Orexin 1 receptor antagonists in compulsive behavior and anxiety: possible therapeutic use.
Front Neurosci, 8: 26. [PMID:24592206]
6. Mould R, Brown J, Marshall FH, Langmead CJ. (2014)
Binding kinetics differentiates functional antagonism of orexin-2 receptor ligands.
Br J Pharmacol, 171 (2): 351-63. [PMID:23692283]
7. Porter RA, Chan WN, Coulton S, Johns A, Hadley MS, Widdowson K, Jerman JC, Brough SJ, Coldwell M, Smart D et al.. (2001)
1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor.
Bioorg Med Chem Lett, 11 (14): 1907-10. [PMID:11459658]
8. Rappas M, Ali AAE, Bennett KA, Brown JD, Bucknell SJ, Congreve M, Cooke RM, Cseke G, de Graaf C, Doré AS et al.. (2020)
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
J Med Chem, 63 (4): 1528-1543. [PMID:31860301]